Intense Sweeteners, Taste Receptors and the Gut Microbiome: A Metabolic Health Perspective

Abstract

Intense sweeteners (IS) are often marketed as a healthier alternative to sugars, with the potential to aid in combating the worldwide rise of diabetes and obesity. However, their use has been counterintuitively associated with impaired glucose homeostasis, weight gain and altered gut microbiota. The nature of these associations, and the mechanisms responsible, are yet to be fully elucidated. Differences in their interaction with taste receptors may be a potential explanatory factor. Like sugars, IS stimulate sweet taste receptors, but due to their diverse structures, some are also able to stimulate bitter taste receptors. These receptors are expressed in the oral cavity and extra-orally, including throughout the gastrointestinal tract. They are involved in the modulation of appetite, glucose homeostasis and gut motility. Therefore, taste genotypes resulting in functional receptor changes and altered receptor expression levels may be associated with metabolic conditions. IS and taste receptors may both interact with the gastrointestinal microbiome, and their interactions may potentially explain the relationship between IS use, obesity and metabolic outcomes. While these elements are often studied in isolation, the potential interactions remain unexplored. Here, the current evidence of the relationship between IS use, obesity and metabolic outcomes is presented, and the potential roles for interactions with taste receptors and the gastrointestinal microbiota in modulating these relationships are explored.

Keywords: gut hormone; gut microbiome; metabolism; non-nutritive sweetener; obesity; sweetener; taste receptor.

Figure 1

Potential interactions between taste receptors (TR), intense sweeteners (IS), the gut microbiome and metabolic conditions. Oral taste receptor expression levels, along with TASR genotypes, determine the palatability or aversiveness of sweeteners, which affects IS intake levels. IS may then activate gastrointestinal T1Rs and T2Rs, which may lead to altered metabolic hormone secretion. Some IS also have an effect on the composition and function of the intestinal microbiome, which may also lead to metabolic alterations. Interestingly, both an altered gut microbiome and certain metabolic disturbances may alter oral taste receptor expression levels. Finally, it is hypothesised that extra-oral taste receptor expression may be altered in response to intestinal dysbiosis, and this may impact the expression of extra-oral taste receptors, resulting in metabolic alterations.